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Mol Genet Metab. 2007 Nov;92(3):229-33. Epub 2007 Aug 13.

A novel complex deletion-insertion mutation mediated by Alu repetitive elements leads to lipoprotein lipase deficiency.

Author information

1
Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan. QFG00550@nifty.com

Abstract

Lipoprotein lipase (LPL) deficiency is a rare autosomal recessive inherited disorder, characterized by marked hypertriglyceridemia, eruptive xanthoma, hepatosplenomegaly, recurrent attacks of pancreatitis, and markedly low or absent LPL activity in postheparin plasma. A majority of LPL deficient patients have been reported to have point mutations in the LPL gene; however, we find a complex deletion-insertion mutation by Alu elements, mobile retrotransposons, in a patient with LPL deficiency. This patient suffered from acute pancreatitis, showed chylomicronemia and lacked detectable LPL activity or mass in her postheparin plasma. Southern blot analysis and long-range PCR of the patient's DNA demonstrated a 2.2-kb deletion encompassing exon 2. Sequence analysis revealed (1) a 2.3-kb deletion between an AT-rich region adjacent to an Alu element in intron 1 and another Alu element in intron 2; (2) an insertion of approximately 150bp 5'-truncated Alu sequence with a poly (A) tail at the deletion point. The inserted sequence belongs to Alu Yb9, the youngest subfamily of Alu elements. The deletion occurred at the consensus cleavage site (3'-A|TTTT-5') without target site duplication. These findings indicated that Alu retrotransposition caused the complex deletion-insertion. The patient was homozygous for this complex mutation, which eliminates exon 2 and leads to LPL deficiency. To our knowledge, the patient is the first case with LPL deficiency due to a complex deletion-insertion mediated by Alu repetitive elements.

PMID:
17706445
DOI:
10.1016/j.ymgme.2007.06.018
[Indexed for MEDLINE]

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